Completion of a structure-activity relationship study of pyrido(2,3-d)-pyrimidine nucleosides will be undertaken. A new approach to the development of highly specific inhibitors of thymidylate synthetase will be initiated. These inhibitors will be various derivatives of N-thymidinylpyrido(2,3-d) and (3,2-d)-pyrimidines. Reduction/oxidation properties of these molecules will be studied.